Search Results (7,122)

Background: Photodynamic therapy (PDT) has emerged as a powerful minimally invasive modality for cancer treatment. However, its efficacy as a monotherapy is often limited by oxygen dependence and limited light penetration. Combining PDT with systemic anticancer drug therapies offers a promising strategy to achieve synergistic effects and overcome resistance. Objective: This review aims to provide a systematic analysis of the mechanisms and clinical potential of combining PDT with chemotherapy, targeted therapy, and immunotherapy, focusing on recent advancements and nanotechnology-based delivery systems. Methods: A comprehensive literature search was performed using PubMed and Scopus databases. The analysis focused on peer-reviewed studies published over the last 10 years addressing synergistic molecular pathways, co-delivery nanoplatforms, and clinical trial outcomes. Results: The combination of PDT with chemotherapy enhances drug accumulation via vascular photosensitization and can overcome multi-drug resistance. Integration with immunotherapy, particularly immune checkpoint inhibitors and tumor vaccines, triggers immunogenic cell death (ICD), leading to systemic antitumor responses. Nanotechnology provides a versatile platform for the targeted co-delivery of photosensitizers and pharmacological agents, significantly reducing systemic toxicity. Conclusions: Combined PDT–drug regimens demonstrate superior therapeutic efficacy compared to monotherapies. Future clinical translation requires the standardization of dosimetry and the development of multifunctional nanomedicines to enable personalized treatment protocols. Full article

Heavy metal contamination of foods remains a persistent global challenge for food safety and public health, driven by industrialization, mining activities, intensive agriculture, and ongoing environmental degradation. This scoping review synthesizes peer-reviewed literature on the occurrence of priority toxic metals—arsenic, cadmium, lead, mercury, and nickel—in food matrices, with emphasis on contamination pathways, analytical detection strategies, and documented human health effects. The reviewed studies reveal widespread accumulation of heavy metals in staple foods, including cereals, vegetables, seafood, and processed products, with concentrations frequently approaching or exceeding international regulatory limits, particularly in regions exposed to strong anthropogenic pressure. Conventional laboratory-based techniques, such as atomic absorption spectrometry and inductively coupled plasma methods, remain the reference standards for quantitative determination and regulatory compliance; however, their application to large-scale or continuous monitoring is often constrained by cost, infrastructure, and operational complexity. Consequently, increasing attention has been directed toward emerging detection approaches, including portable X-Ray fluorescence, Raman/SERS spectroscopy, electrochemical biosensors, electronic tongues, and in situ magnetic measurements, as complementary tools for rapid screening and field-based surveillance. Among these, environmental magnetism and in situ magnetic techniques stand out as non-destructive, low-cost proxies capable of identifying metal-associated particulate contamination linked to food production systems. Chronic dietary exposure to heavy metals is consistently associated with neurotoxicity, nephrotoxicity, carcinogenicity, and oxidative stress, underscoring the need for integrated, multi-tiered monitoring frameworks to support early detection, risk assessment, and prevention. Full article

Calcium channel blockers (CCBs) are frequently used in the emergency department and intensive care unit for a wide range of critical conditions, including atrial fibrillation, hypertensive emergencies, acute pulmonary edema with sympathetic crashing, pulmonary hypertension, and vasospastic syndromes. However, their toxicity can lead to significant hemodynamic compromise, underscoring the importance of understanding their pharmacologic effects and safety profile. This review summarizes the current applications of CCBs in critically ill patients, evaluates their safety in congestive heart failure, and highlights emerging therapeutic roles and recent advances in the management of CCB toxicity. Full article

Metals are an essential part of the life of all organisms because they participate as an essential part of diverse components, especially as enzymatic cofactors. In humans, there are metals that are trace elements and therefore are required for the proper functioning of different biological processes, so they must be present in cells and tissues. However, when the organism is overexposed, those same essential metals—in high concentrations that become toxic—cause imbalances or overt pathologies. On the other hand, there are metals that are not essential in humans, so their presence and accumulation in the organism can cause adverse effects. In this review we focus on the essentiality and toxicity of the main trace metals such as iron, zinc, copper, manganese, chromium, cobalt, molybdenum, and nickel, as well as on the toxicity of metals such as vanadium, cadmium, and lead that are not essential for humans. In addition, the report describes the main mechanisms by which metals exert their toxic effects on the body, as well as the primary sources of pollution through which they are released into the environment. Full article

Cancer remains one of the leading causes of morbidity and mortality worldwide, and despite major advances in surgery, chemotherapy, radiotherapy, and immunotherapy, important therapeutic limitations persist, including systemic toxicity, therapeutic resistance, and poor drug penetration into hypoxic tumor regions. These challenges have renewed interest in alternative biological strategies, particularly the use of bacteria and bacterial toxins as antitumor agents. Certain bacterial species possess intrinsic tumor-targeting properties, including the ability to selectively colonize hypoxic and necrotic regions of solid tumors that are poorly accessible to conventional therapies. This review provides a comprehensive analysis of the mechanisms underlying bacteria-mediated anticancer activity, including selective tumor colonization, direct oncolysis, immune activation, and toxin-mediated cytotoxicity. Both obligate anaerobes (e.g., Clostridium and Bifidobacterium) and facultative anaerobes (e.g., Salmonella, Escherichia coli, and Listeria monocytogenes) are examined for their tumor-targeting potential. In addition, we discuss the oncological applications of several bacterial toxins and toxin-derived therapeutic constructs, including Cytolysin A (ClyA), Clostridium difficile toxin B (TcdB), diphtheria toxin, Pseudomonas aeruginosa exotoxin A, and Clostridium perfringens enterotoxin (CPE). Emerging strategies such as recombinant immunotoxins and bacterial-directed enzyme prodrug therapy (BDEPT) are also reviewed. Finally, current translational challenges, including pharmacokinetic limitations, immune clearance, and biosafety considerations, are analyzed, highlighting future directions for integrating bacteria-based platforms into next-generation cancer therapies. This approach reflects the growing interest in microbial strategies for oncology and underscores the potential of bacteria and their toxins as innovative tools in the development of targeted anticancer therapies. Full article

Heart failure (HF) is a leading cause of morbidity and mortality worldwide, and its co-occurrence with psychiatric disorders poses significant therapeutic challenges. This narrative review examines the safe use of psychopharmacological agents in patients with HF, focusing on mood stabilizers (particularly lithium) and antipsychotics. We summarize clinically relevant pharmacokinetic and pharmacodynamic interactions between these agents and guideline-directed HF therapies, including ACEIs, ARBs, ARNIs, beta-blockers, MRAs, SGLT2 inhibitors, and diuretics. Lithium is particularly prone to interactions due to its narrow therapeutic index and dependence on renal sodium handling, with RAAS inhibitors, thiazide diuretics, and SGLT2 inhibitors increasing the risk of toxicity. Antipsychotics are associated with QT prolongation, orthostatic hypotension, and electrolyte disturbances, with substantial variability between agents. This review highlights key clinical risks, provides a practical summary of drug interactions, and outlines principles for individualized, multidisciplinary management. Care requires coordinated cardiology–psychiatry collaboration, careful drug selection, and assessment of renal function, electrolytes, drug levels, and ECG parameters. Further studies and improved guideline integration are needed. Full article

Arginase 1 (ARG1) deficiency (ARG1-D) is a rare genetic disorder due to loss of ARG1, the final enzyme in the urea cycle. ARG1-D hepatocytes are impaired in converting arginine into urea, resulting in elevated peripheral arginine and ammonia, which leads to progressive neurological symptoms. Current therapeutic strategies mainly focus on managing plasma arginine and ammonia level, but long-term outcomes remain poor. While no approved treatment specific for ARG1-D is available in the United States, a recombinant protein-based enzyme replacement therapy is available in Europe. Recently, extracellular vesicles (EVs) are emerging as a powerful therapeutic vehicle. By using Capricor’s StealthX^TM platform, EVs were engineered to express human ARG1 on their surface or encapsulated within. Regardless of their localization on the EV membrane, nanograms of ARG1 carried by EVs were biologically active and able to convert arginine into urea as potent as micrograms of human recombinant ARG1 (rHuArg1). Furthermore, ARG1-encapsulating EVs (STX-Arg1-in) were able to deliver ARG1 intracellularly but not EVs carrying ARG1 on their surface or rHuArg1. STX-Arg1-in EVs were further evaluated in a series of in vivo studies, and the results showed that STX-Arg1-in EVs were non-toxic and able to restore arginase activities in the liver of Arg1^−/− mice, which led to a lowered plasma arginine concentration similar to that in wild-type mice. Most importantly, Arg1-in EVs expanded the lifespan of the lethal neonatal Arg1 deficiency mouse model. Taken together, our data suggested StealthX^TM-engineered STX-Arg1-in EVs have a better safety profile due to the extremely low dosage and have great potential as a novel enzyme replacement strategy for patients suffering from ARG1-D. Significance statement: Intracellular delivery of recombinant protein and improved llifespanare endpoints of successful enzyme replacement therapy for the treatment of ARG1-D. Using the StealthX platform, a fully functional ARG1 enzyme was engineered to be carried inside of the extracellular vesicles, which allowed for the intracellular delivery of ARG1 protein in vitro and in vivo, with an improvement of lifespan in a lethal neonatal mouse model of Arg1 deficiency. More importantly, no toxicity was observed, and efficacy was achieved with a low dose, setting the base for an improved therapeutic approach. Full article

Since their initial discovery in 2003, carbon quantum dots (CDs) have attracted significant attention due to their unique optical properties and potential biomedical applications. This review critically examines the past 20 years of research on CDs, with a particular focus on cytotoxicity studies from the last decade. CDs, typically less than 10 nm in size, have been synthesized from various organic and inorganic precursors using multiple methods, including hydrothermal, microwave, and chemical reduction techniques. Their properties can be finely tuned by modifying synthesis parameters and incorporating dopants. The preliminary studies on the biological effects of CDs were published in 2013, highlighting their antibacterial properties and low toxicity in certain contexts. Subsequent research has explored their bioactivity, including their application in drug delivery, bioimaging, and photothermal therapy. However, the cytotoxicity of CDs remains a critical area of investigation. Further studies have demonstrated that surface functional groups, charge, concentration, and size significantly influence their interaction with biological systems. For instance, CDs with positive surface charges exhibit higher cellular uptake and greater cytotoxicity compared to their negatively charged counterparts. In vivo studies utilizing animal models such as zebrafish, mice, and planarians have provided valuable insights into the potential toxicological impacts of CDs. The results indicate that while CDs generally exhibit low toxicity at certain concentrations, high doses can lead to adverse effects, including oxidative stress, organ damage, and disrupted cellular functions. Notably, the route of administration (oral, intravenous, or intraperitoneal) also affects the observed toxicity profiles. The goal of this review is to integrate the results of various studies to provide a balanced perspective on the potential risks and benefits of CDs, guiding future research and applications in nanomedicine. This review underscores the necessity for standardized and comprehensive toxicological evaluations of CDs to fully understand their safety and efficacy for biomedical applications. Full article

IgA nephropathy is the most common primary glomerulonephritis worldwide and a leading cause of chronic kidney disease and kidney failure, with geographic and ancestral variation and a course ranging from asymptomatic urinary abnormalities to progressive loss of kidney function. This narrative review links the multi-hit model to risk stratification, biomarkers, current management, and emerging therapies, and highlights implementation gaps. Risk assessment is longitudinal, prioritizing proteinuria and estimated glomerular filtration rate trajectories and integrating Oxford MEST-C, prediction tools, and biomarker and multi-omics approaches, while recognizing limitations in histologic reproducibility and model calibration. Current management is anchored in optimized supportive care aimed at sustained proteinuria reduction and kidney protection, including intensive blood pressure control with maximal tolerated renin–angiotensin system blockade, dietary sodium restriction and lifestyle measures, and sodium–glucose co-transporter 2 inhibitors for eligible patients. For selected higher-risk patients with persistent proteinuria despite optimized supportive care, immunomodulatory strategies are discussed, including systemic corticosteroids and targeted-release budesonide (Nefecon), emphasizing structured toxicity risk mitigation and cautioning against assuming interchangeability among alternative oral budesonide formulations. Emerging therapies are organized around mechanism-aligned targets across the BAFF/APRIL axis, complement pathways, and endothelin-based approaches, with growing interest in sequencing and combination regimens layered on supportive care. Key gaps include reliance on surrogate endpoints, limited long-term durability and safety data, and uneven evidence for special populations. Full article

Background/Objectives: TCIRG1-associated infantile osteopetrosis is a severe hereditary disorder caused by impaired osteoclast function, leading to osteosclerosis, hematological abnormalities, neurological complications, and early mortality. Early diagnosis and intervention are critical. Methods: A literature-based analysis was performed on clinical manifestations, outcomes of allogeneic hematopoietic stem cell transplantation (HSCT), immunomodulatory therapy, and experimental gene therapy and cell-based approaches, including lentiviral vectors and patient-derived induced pluripotent stem cells (iPSCs). Results: Allogeneic HSCT is the only established curative therapy, restoring osteoclast function and preventing severe complications. Early transplantation with HLA-matched donors and myeloablative conditioning provides optimal outcomes. Interferon γ1b can transiently enhance osteoclast activity but is not curative and shows variable efficacy. Preclinical studies demonstrate that lentiviral TCIRG1 delivery and transgenic correction in patient-derived iPSCs restore osteoclast function and bone resorption, with stable gene expression and minimal toxicity. Base and prime editing approaches offer potential for precise correction of single-nucleotide TCIRG1 variants, minimizing risks associated with double-strand DNA breaks. Conclusions: Allogeneic HSCT remains the standard therapy for TCIRG1-associated infantile osteopetrosis. Gene therapy and cell-based strategies represent promising adjuncts or alternatives, potentially avoiding immune-related complications and expanding therapeutic options. Further studies are needed to ensure safety, stable engraftment, and long-term efficacy, supporting translation of gene therapy into clinical practice. Full article

It is well-known that immune checkpoint inhibitors (ICIs) can lead to uncommon but potentially life-threatening immune-related adverse events (irAEs) such as checkpoint-inhibitor pneumonitis (CIP). Early recognition, identification, and treatment are crucial with regard to decreasing toxicity from ICIs. However, there is a discrepancy in the incidence rates between the clinical trials and postmarketing studies. Several postmarketing studies have developed early detection methods and identified new risk factors in developing CIP. Thus, in this narrative review, we aim to review these incidence rates, early detection methods, and clinical risk factors for CIP in NSCLC patients, which could help to improve CIP diagnosis and management for enhanced NSCLC care. Major clinical trials and postmarketing studies of CIP incidence, early detection methods, and risk factors in NSCLC were reviewed. A wide array of potential risk factors has been implicated in the development of CIP in NSCLC, such as having preexisting interstitial lung disease, receiving PD-1 inhibitors, receiving combination ICI therapy instead of ICI monotherapy, lower pretreatment hemoglobin and albumin levels, increased baseline plasma IL-8 levels, and impaired baseline pulmonary function. Full article

Background: Prostate cancer (PCa) is the leading male urinary malignancy globally. Our previous article demonstrated the anti-PCa activity of Euphorbia humifusa Willd water extract (EHW) and some of its compounds via downregulating AR expression, but the anti-PCa active compounds from Euphorbia humifusa Willd (EH) and their mechanisms of action are yet to be clarified. Thus, the current article studied the in vitro anti-PCa effects of 3,3′-di-O-methylellagic acid (3,3′-di-O-Me-EA) derived from EHW and the related mechanism involved. Methods: 3,3’-di-O-Me-EA was isolated from EHW applying bioassay-guided fractionation. The spectroscopic methods were used to determining the structure of 3,3′-di-O-Me-EA. The drug-likeness and ADMET properties (absorption, distribution, metabolism, excretion, and toxicity) of 3,3′-di-O-Me-EA were analyzed in silico. Molecular docking and real-time surface plasmon resonance (SPR) analysis were performed to measure the interaction of 3,3′-di-O-Me-EA and VDAC1 protein. The viability and apoptosis of 22RV-1 and DU145 PCa cells were determined using MTT and Annexin V-FITC staining assay, respectively. q-PCR and Western blot experiments were used to analyzing the gene and protein expressions of VDAC1. Results: 3,3′-di-O-Me-EA was isolated and purified from EHW with a purity of ≥90.06%, and its structure was identified by HRTOF mass, NMR, and an authentic standard. In silico ADMET analysis indicated its favorable drug-like and pharmacokinetic properties. Molecular docking and SPR results confirmed that 3,3′-di-O-Me-EA could bind with the VDAC1 protein. Moreover, 3,3′-di-O-Me-EA dose- and time-dependently inhibited 22RV-1 and DU145 PCa cell viability, and induced apoptosis in a dose-dependent manner (p < 0.05). RT-qPCR and Western blot results showed that 3,3′-di-O-Me-EA dose-dependently up-regulated VDAC1 gene and protein expression levels in 22RV-1 and DU145 cells (p < 0.05). Meanwhile, in VDAC1-depleted 22RV-1 and DU145 cells, 3,3′-di-O-Me-EA down-regulated VDAC1 gene and protein expression levels, increased cell viability, and inhibited apoptosis compared to 22RV-1 and DU145 cells (p < 0.05). Furthermore, 3,3′-di-O-Me-EA enhanced VDAC1 gene and protein expression levels, inhibited cell viability, and induced apoptosis in VDAC1-overexpressed 22RV-1 and DU145 cells compared with 22RV-1 and DU145 cells (p < 0.05). Overall, EH active compound 3,3′-di-O-Me-EA may inhibit viability and induce apoptosis of 22RV-1 and DU145 PCa cells via up-regulating VDAC1 gene and protein expression levels. Conclusion: The results indicated that the 22RV1 and DU145 PCa cell viability inhibitory effects of 3,3′-di-O-Me-EA isolated from EH may be mediated by induction of apoptosis through up-regulation of VDAC1 gene and protein expression levels. Full article

The increasing presence of contaminants of emerging concern (CECs) in surface and groundwater is a global concern due to their toxicity, persistence, and bioaccumulation, which lead to undesired effects. Conventional wastewater treatment processes are unable to remove these CECs, necessitating advanced treatment strategies to remove them effectively. Among advanced strategies, photocatalytic membrane treatment has attracted considerable interest among researchers. This review critically examines the fundamental principles governing the performance of photocatalytic membranes. It identifies significant challenges, including photocatalyst leaching, light accessibility, intermediates’ toxicity, and scalability of synthesis and immobilisation techniques. It explains why these factors significantly hinder long-term stability, scalability, and practical deployment of photocatalytic membrane systems and provides potential solutions. Through gap analysis, the review has identified rigorous techno-economic analysis, real-world wastewater validation, and systematic toxicity assessment of degradation intermediates as areas of further study. These targeted actions provide clear pathways to enhance the viability, safety, and commercial readiness of photocatalytic membrane systems. Full article

Myrciaria floribunda is a plant found in the Northeast region of Brazil with several insecticidal properties that remain little explored. In this sense, this study aims to investigate the harmful effects of essential oil (EO) from M. floribunda leaves against Sitophilus zeamais, an important corn pest. The EO was applied in toxicity tests by fumigation, contact, and ingestion, as well as in in vitro assays to evaluate its effects on the activity of the enzymes α-amylase, trypsin, and acetylcholinesterase. Chromatographic analysis of the oil revealed (E)-caryophyllene (56.41%), viridiflorol (4.02%) and α-selinene (3.85%) as the main compounds. The essential oil (EO) showed fumigation toxicity, with an LC₅₀ of 3.2 μL/L of air, and (E)-caryophyllene with an LC₅₀ of 3.97 μL/L of air. The EO inhibited insect feeding, altering growth rate and feed conversion efficiency starting at 62.5 μL/g. In this study, an increase in amylase and acetylcholinesterase (AChE) activity was observed. This increase in AChE activity may cause an imbalance in the nervous system, leading to insect death. Thus, the EO of M. floribunda may serve as an alternative for the control of S. zeamais in stored corn and help prevent significant post-harvest losses for farmers. Full article

Mitochondria are essential organelles that perform irreplaceable functions in neurons. The degeneration of neurons in Alzheimer’s disease (AD) is associated with mitochondrial damage, and Tau pathology represents a significant pathogenic factor in AD. However, the relationship between Tau and mitochondrial dysfunction during neuronal degeneration remains unclear. In this study, we investigated the effects and mechanisms by which extracellular Tau aggregates induce neuronal mitochondrial damage and dysfunction. The results showed that extracellular Tau aggregates lead to structural damage of mitochondria in SH-SY5Y cells and disrupt mitochondrial homeostasis. Extracellular Tau aggregates can also cause mitochondrial oxidative stress and inhibit oxidative phosphorylation in SH-SY5Y cells. Concurrently, extracellular Tau aggregates promote neuronal death through an increase in cytochrome C, mtDNA leakage and activation of the cGAS/STING pathway. We also explored the effects of a single-chain variable fragment antibody (scFv T1) and found that scFv T1 alleviated mitochondrial damage and dysfunction by inhibiting the formation of Tau aggregates. These findings suggest that targeting Tau pathology may be crucial to address neuronal mitochondrial impairment and that reduction of the toxicity associated with extracellular Tau aggregates could help slow Tau pathology progression. Full article